Signaling proteins of the human liver fluke, Opisthorchis viverrini Cholangiocarcinoma (CCA) – cancer of the bile ducts – is associated with chronic infection with the oriental liver fluke, Opisthorchis viverrini. Despite being one of only three eukaryotic organisms designated as a 'Group 1 carcinogen" by the International Agency of Research on Cancer (IARC), research into the transcriptome and genome of this enigmatic parasite is still in its infancy. A gene discovery project for O. viverrini using the expressed sequence tag (EST) approach was begun in 2007 (Laha, 2007). Among other genes, EST's representing putatively secreted or transmembrane proteins with known roles in tumor induction and progression were identified. The characterization of three of these secreted or transmembrane proteins, an orthologue of caspase 9, fibroblast growth factor receptor substrate 2 (FRS2), and transforming growth factor – β receptor type 1 (TGF-βR1) are presented here. All three are members of signaling pathways involved in practically all aspects of cell behavior and homeostasis (Cooper and Hausman, 2007).
Disruption of signaling pathways controlling homeostasis and physiologic activities have been shown to result in pathology in many species. The O. viverrini signaling proteins in this dissertation are all factors in essential signaling pathways whose roles within the parasite have yet to be discovered but may provide future targets of intervention for chemotherapeutic and/or vaccine targets. The findings presented here characterizing, to varying degrees, O. viverrini caspase 9, FRS2, and TGF-βR1 can be expected to provide a foundation for further studies into the physiology of the human liver fluke.
|Advisor:||Brindley, Paul J.|
|Commitee:||Betheny, Jeffrey M., Hawdon, John M., Loukas, Alexander, O'Neil, Michael T.|
|School:||The George Washington University|
|School Location:||United States -- District of Columbia|
|Source:||DAI-B 74/01(E), Dissertation Abstracts International|
|Subjects:||Molecular biology, Parasitology|
|Keywords:||Caspase 9, Fluke, Liver, Opisthorchis viverrini, Proteins, Signaling|
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